The classification of the indolent B cell lymphomas closely follows the notion that B cell neoplasms tend to recapitulate the stages of normal B cell maturation. They do frequently lack further differentiation capacity, thus being similar to “frozen” stages of lymphocyte development . In normal B lymphocyte development, naïve and often CD5+ B cells circulate in the blood and also colonize the primary follicles and follicular mantle zones of the B cell areas of the lymph node. Mantle cell lymphoma (MCL) is the putative neoplastic counterpart of these naïve CD5+ B cells. Upon antigen contact, the naïve B cells migrate into the follicle, proliferate, and form the germinal center (GC). In this specialized lymphoid compartment, important modifications of the B cell receptor repertoire take place, such as somatic hypermutation of the immunoglobulin-heavy (IGH) and light-chain variable (IGV) gene regions, class switching, and receptor editing. These modifications in the immunoglobulin genes result in refinement of the specificity of the encoded antibody (affinity maturation) and are the prerequisite for the high specificity of the B cells in the secondary immune response. Ongoing IGV region gene mutation is a hallmark of both reactive germinal centers as well as the GC of follicular lymphoma (FL), thus making FL the archetype of a germinal-center-derived lymphoma. In the late GC reaction, centroblasts differentiate into centrocytes, and those cells that have acquired high-affinity IGV mutations will be rescued from apoptosis via re-expression of BCL2 as well as IRF4/MUM1. Centrocytes then differentiate into either memory B cells or plasma cells, with post-germinal center B cells being characterized by highly mutated IGV genes, without ongoing mutations. Post-germinal center memory B cells circulate in the peripheral blood and colonize the follicular marginal zones of lymph nodes, spleen, and mucosa-associated lymphoid tissues (MALT). Marginal zone lymphomas of MALT, splenic, and nodal types correspond to post germinal center memory B cells, with an inherent propensity for homing and proliferation within their respective tissue sub-compartments (e.g., the marginal zone). Plasma cell myeloma is the neoplastic equivalent of a bone-marrow-homing post-GC, terminally differentiated B cell. Apart from showing biological characteristics of their corresponding normal cell type as delineated above, mature indolent B cell lymphomas are also those lymphoid neoplasias that are most intimately associated with distinct chromosomal aberrations, such as the t(11;14) in mantle cell lymphoma or the t(14;18) in FL. In most instances, however, these primary aberrations do not suffice to fully transform the cell, but are a prerequisite for further tumor development, e.g., by prolonging the lifespan of a cell that can then acquire secondary chromosomal alterations.